Vacuolar-type H+-translocating ATPase (V-ATPase)

Vacuolar-type H+-translocating ATPase (V-ATPase) is a large, multi-subunit rotary proton pump complex found in the membranes of intracellular organelles and the plasma membrane of specialized cells. It is composed of two main regions: the peripheral V1 domain, responsible for ATP hydrolysis, and the integral V0 domain, responsible for proton translocation across membranes[1][2][3]. V-ATPases play a fundamental role in acidifying various intracellular compartments—such as endosomes, lysosomes, and secretory vesicles—which is critical for protein degradation, receptor-mediated endocytosis, and neurotransmitter loading[2][3]. The complex is also essential in various differentiated cells for physiological processes such as bone resorption, urinary acidification, and tumor cell invasion[2]. V-ATPase dysfunction is associated with a spectrum of human diseases, including cancer, osteopetrosis, renal tubular acidosis, and sensorineural deafness[1][2]. Several natural and synthetic inhibitors target V-ATPase and are under investigation as potential anticancer or antimicrobial agents[2]. Key therapeutic challenges involve selective targeting to avoid systemic disruption of vital pH regulatory processes.

Other names

Vacuolar H+-ATPaseV-ATPaseVacuolar ATPaseVacuolar proton pumpV-type ATPase

Inhibition of ATP hydrolysis Blockade of proton translocation Disruption of organelle acidification Prevention of lysosomal/autophagic function in cancer